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March 18, 2021
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Experts offer opinions on global trends in retina, part 2

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In conjunction with the annual ASRS Preferences and Trends survey, retina specialists in Asia-Pacific, Africa and Middle East, Central-South America and Europe were invited to participate in the Global Trends in Retina Survey.

In part 2 of this cover story on the 2020 survey highlights, thought leaders from around the world discuss different approaches to monitoring patients, clinical utility of OCT angiography (OCTA), expectations about new, longer-lasting therapeutic options and changing attitudes in retinal surgery. (Click here to read part 1.)

Gemmy Cheung, MD
Even though OCT drives most decision-making, eye examination may identify other disease activity or causes for vision loss, according to Gemmy Cheung, MD, FRCOphth.

Source: Gemmy Cheung, MD, FRCOphth

The survey highlighted significant differences in the approach to monitoring patients who require chronic anti-VEGF therapy. While the proportion of retina specialists who do not routinely examine the eye in addition to performing OCT at every visit is low in other regions (down to 11% in Asia and Africa-Middle East), about 40% of U.S. specialists seem to be comfortable with performing OCT alone.

While it has not been established whether the pandemic affected responses in individual countries, there are reasons beyond COVID-19 that make U.S. specialists less likely to routinely perform eye exams, according to Dean Eliott, MD, chair of the American Society of Retina Specialists International Affairs Committee.

“We are not routinely reimbursed for performing an eye exam at the time of intravitreal injection. During an injection visit, most retina specialists carefully look at the OCT and sometimes perform an exam, and then they use the appropriate billing modifier in an attempt to get reimbursed for the exam. However, if you do this too often, you are likely to get audited. Thus, I often do a brief exam and don’t bill for it. Clearly, we have to examine our patients, but examining them at every or almost every office visit and billing for it would be extreme, in my opinion,” he said.

“We may rely on just OCT more often now because of the risk of COVID-19 infection, but normally we prefer to do a complete examination,” José Antonio Roca, MD, professor at Cayetano Heredia Peruvian University in Lima, Peru, said.

So does Ursula Schmidt-Erfurth, MD, PhD, professor at the Medical University of Vienna, Austria, who believes that a complete eye exam is all the more important now that injection intervals are spread out to 2, 3 or even 4 months.

“Definitely I want to examine a retina that has one of the most severe diseases. There is still too much interobserver variability in interpreting OCT, as we have seen in clinical trials. In the CATT study, clinicians less frequently identified OCT macular fluid than the reading center, and there was discrepancy in nearly 30% of the cases between clinicians’ decisions regarding treatment and the reading center’s determination of macular fluid status,” she said.

Ursula Schmidt-Erfurth, MD, PhD
Ursula Schmidt-Erfurth

Schmidt-Erfurth also said that central retinal thickness is not a good parameter, as it has a low correlation with the real amount of fluid.

“In our department, we use deep learning methods for localization and quantification of fluid, and this gives us a very accurate evaluation of OCT. Once these automated algorithms become publicly available, every ophthalmologist will be able to measure the fluid in the retina with a mouse click,” she said.

Changing habits during pandemic

Two other specialists said that examining the eye at every single visit may be more of a habit than a necessity, but it may have advantages.

“Most of us do it partly because it is traditional. We feel historically more secure if we do a full examination. However, although OCT drives most of the decisions, when we examine the eye, we may pick up other causes for vision loss, particularly subtle bleeding or other disease activity,” Gemmy Cheung, MD,FRCOphth, professor at National University of Singapore, said.

“I do an OCT at every visit and still examine every patient. I think I do it mainly to check if they didn’t develop something else, like cataract or retinal tears,” Anat Loewenstein, MD, MHA, professor at Tel Aviv University, Israel, said.

The COVID-19 pandemic has disrupted routine practices, and new protocols have been created to minimize the risk for infection.

Anat Loewenstein, MD, MHA
Anat Loewenstein

“We are doing more injection-only visits. With new patients who need loading, we do a full examination and then book them for two injection-only visits without even an OCT if they don’t report worsening. They get the next full examination at the fourth visit. For patients who are already undergoing treatment and are stable, I schedule an injection at their established interval and perform an examination during every other injection visit,” Cheung said.

Loewenstein has intensified her studies on home-based OCT monitoring and is verifying how this compares with the routine practice of performing an OCT and examining patients in the office.

“Looking at many cases, we found that home OCT monitoring compared to routine OCT and eye examination in the office, including VA, leads to the same treatment decisions,” she said. “So, on one hand I am still old-fashioned in the way I look every time at every patient, and on the other hand, I am proving that it is not necessary. I think that definitively we are moving in this direction.”

“The U.S. approach is quite reasonable, and I imagine that we will progressively transit to doing less traditional examination and doing more OCT-based or even just injection-only visits,” Cheung said.

New therapies

There is no doubt that everyone would welcome more durable drugs and delivery systems. The highest rate of those who hope that they will reduce patient load in the near future is in Europe (75.6%), followed by Asia-Pacific and Africa-Middle East (71%). Expectations are more tepid in the U.S. (54.5%) and Latin America (62.3%).

“What we need is a drug with more powerful, long-lasting effect, like brolucizumab, which we can administer ideally every 4 or 6 months,” Roca said.

However, he thinks that port delivery systems are not an appropriate strategy for Latin America because there is a high risk for infection if patients are not compliant with good hygiene practices. In many areas, access to clean water and improved sanitation is poor. Gene therapy, which potentially provides lifelong benefits with a single therapeutic administration, would be a more ideal strategy in this environment.

Dean Eliott, MD
Dean Eliott

“In the U.S., most retina specialists are overwhelmed with patients who need treatment. In this time of COVID, we want to reduce the number of elderly patients sitting in our waiting room, even with the appropriate social distancing. Thus, we would welcome any development that decreases the treatment burden,” Eliott said.

Loewenstein favors slow-release devices as a technology that may dramatically change the way patients are managed.

“This is definitively true for DME, DR and RVO, but also for AMD. I think we will have much less volume load, and home OCT and other technologies will also reduce the number of monitoring visits,” she said.

“We have quite a few promising options on the horizon,” Cheung said. “We have Beovu (brolucizumab, Novartis), although there are some safety concerns, and we have the Port Delivery System (PDS, Genentech). We look forward to faricimab (Genentech), which has reported favorable results in phase 3 DME and nAMD trials.”

New drugs and delivery systems will reduce patient volume but will still not be enough to significantly reduce the backlog of untreated or undertreated patients worldwide, according to Schmidt-Erfurth.

“There is a lot we have to catch up with. Real-world studies and WHO data have shown that most patients in the world are undertreated and even undetected. I don’t think our volume of work will be reduced, but we will be able to treat more patients. AMD is increasing as people are getting older, DME is increasing because diabetes is a pandemic, and hopefully some treatment will become available for geographic atrophy, further increasing the number of patients we will be taking care of,” she said.

OCT angiography

Outside the U.S., the majority of retina specialists use or are planning to use OCTA soon and believe it is critical in the management of patients. The percentage of those who have access to it but do not find it useful is on average 15%. Conversely, the majority of U.S. respondents either have access to it but do not find it useful in practice (30%) or do not have access to it and do not plan to get it soon (28.7%). Only 30%, less than half than the average in other regions, have access to it and believe in its clinical utility.

“I was surprised to see such big differences between the U.S. and outside the U.S. Many of us believe that OCTA is a very useful research tool used to advance our understanding of retinal vascular disease, but it does not affect clinical decision-making that often. Maybe outside the U.S. it is different, since in some instances they appear to use OCTA in place of fluorescein angiography. I believe that fluorescein angiography still has a role, although somewhat limited compared to the past,” Eliott said.

The latest upgrades in the technology have improved image quality, partly overcoming the problem of imaging artifacts and segmentation errors, but still Eliott believes that OCTA is useful in a minority of patients.

“In a few cases it does help to determine my treatment choice, but most of the time standard OCT provides sufficient information,” he said.

According to Roca, the limited use of OCTA in the U.S. may also be related to reimbursement issues.

“I think it is a very good and useful tool. I use it a lot for diabetic patients and myopic membranes,” he said.

“I believe there is not yet a specific billing code for OCTA in the U.S., and therefore our colleagues there cannot charge for this test, whereas around the world, we have a more flexible billing system,” Cheung said.

She finds it useful for retinal vascular diseases and vein occlusion in diabetes, in which it helps to decide whether or not to intervene with panretinal photocoagulation. For choroidal neovascularization, it is also useful, but there are issues such as artifacts and segmentation errors that take a long time to sort out.

“For instance, in case of a large pigment epithelial detachment (PED), large hemorrhages or [polypoidal choroidal vasculopathy], OCTA does not perform that well. The need to clean up the segmentation remains a very time-consuming problem. For conditions that are above the retinal pigment epithelium (RPE) and are not disturbed by PED, it works very well, but for conditions that are under the RPE, it continues to be not as user-friendly as we would like it to be,” she said.

“I think that the hype about OCTA has already vanished in the U.S. because the therapeutic utility is limited so far,” Schmidt-Erfurth said. “For [wet] AMD, we know that CNV size or any particular feature of CNV visible on OCTA is not relevant for disease activity. What we treat is fluid, and we see fluid by regular, standard OCT.”

However, she believes that widefield OCTA, once it becomes available, will play an important role in diabetic retinopathy.

In Israel, OCTA is widely accessible, but the interest in this imaging modality has decreased because it has not been shown to make a real change in the clinical management of patients, according to Loewenstein.

“If you look at meeting programs, also excluding 2020 that has been a very particular year, it is quite clear that the interest was high until 2018 and then dropped. In 2019, there were very few presentations on OCTA in retina subspecialty days as compared with previous years. Research-wise, it teaches us a lot, but in very few cases it affects our clinical decision-making,” she said.

Silicone oil and facedown positioning

Everywhere, but definitely more in the U.S., retina surgeons showed a preference for lower-viscosity silicone oil, which is easier to introduce and remove through small-gauge cannulas, but they still keep the higher-viscosity option open for specific cases.

“Most of us perform small-gauge surgery and therefore use 1,000 cs in the vast majority of cases. But in some cases, I do use 5,000 cs,” Eliott said.

“In my department, we are divided. I use only 1,000 cs, and my two colleagues use 5,000 cs. We have seen no difference in the results, neither in emulsification rate nor in retinal reattachment rate, side effects or IOP rise. So, it is just a matter of surgeon preference. The only difference is that the 5,000 cs cannot be removed by hand,” Loewenstein said.

Schmidt-Erfurth said that silicone oil is used in fewer cases nowadays, down to 1% in retinal detachment (RD).

“It remains an option for very severe diabetic tractional retinal detachment, and I only use 1,000 cs silicone oil,” she said.

Attitudes toward facedown positioning have changed remarkably over the years.

“We used to force our patients to a strict 2-week facedown 20 years ago, but nowadays 5 days is the maximum in my country,” Loewenstein said.

“I usually recommend 5 days of facedown recovery. No more than 5 days,” Roca said.

The questionnaire showed that 5 to 7 days is the most common choice, with quite a number of surgeons opting for 3 to 4 days.

“Things have progressively changed. Many years ago, people were recommending 2 weeks of facedown positioning for macular holes, then it was reduced to 1 week and now to less than 1 week, and some people don’t even use facedown positioning at all. Personally, I recommend 3 days, unless it is a recurrent macular hole, a very large hole or a highly myopic hole, for which I do 5 days,” Eliott said.

“One day, and that’s it. Maybe two in specific cases,” Schmidt-Erfurth said.

Scleral depression

Scleral depression at the end of macular surgery is performed by the majority of respondents in the U.S. (73.5%) and Europe (61.3%), by about half in Central America (55.6%) and Africa-Middle East (49.1%), and in a lower proportion in Asia-Pacific (41.4%).

Eliott said he was happy to see that most surgeons do scleral depression but unhappy that not every doctor does it 100% of the time because it is an easy and quick extra step that can prevent severe complications.

“If you have a severe postoperative complication in a macular surgery case, that would be RD. It is a very rare complication, but you can make it as close to zero as possible if you carefully examine the peripheral retina at the end of the case. If you find a retinal break, you have the perfect opportunity to treat it with laser and maybe a gas bubble as well. I teach my trainees that scleral depression is a critical step of every procedure,” he said. “If I were undergoing macular surgery, I would want my doctor to spend a couple of minutes at the end of the case carefully looking to attempt to prevent this severe complication.”

“I rarely see holes at the end of the case. Nevertheless, if I miss a hole, it will be very disappointing for a patient that came for uncomplicated macular surgery, didn’t even get anesthesia and then a few weeks later experiences retinal detachment. Scleral depression is fast and adds a lot of safety,” Schmidt-Erfurth said.

Loewenstein said she continues to perform scleral depression, although in the last 10 years, she has not had any iatrogenic tears.

“We have now better techniques, better instruments, and smaller and smaller gauge, so it is less important than it was in the past, but it takes a minute or so, and I still do it,” she said.

She remembers a nightmare case she dealt with when she had just come back from her fellowship in the U.S.

“I found myself operating on a very important donor to our hospital. I did the surgery and then indented the sclerotomy, and not only did I see a tear, but also a retinal detachment I had created. I repaired it, and what was meant to be a small surgery became a mega-surgery. I did everything I could possibly do, including a complete vitrectomy,” she said. “Although we have better systems now, and tears and detachments happen less frequently, I would always recommend young surgeons not to miss a small maneuver that saves them from running into big trouble.”

Click here to read the Point/Counter to this Cover Story.